I. Field of the Invention
The present invention relates to compositions comprising therapeutic nucleic acids that target SMAD4 gene expression, lipid particles comprising one or more of the therapeutic nucleic acids, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles (e.g., for treating anemia of inflammation in humans).
II. Description of the Related Art
Anemia of inflammation (sometimes called anemia of chronic disease, or anemia of inflammatory response) is a form of anemia seen in chronic illness (e.g. chronic infection, chronic immune activation, or malignancy), and is the most common anemia found in hospitalized patients. Anemia of inflammation is abbreviated herein as “AI”. Although there may be more than one underlying cause of AI, it appears likely that the syndrome is largely the result of the production of hepcidin, a protein that regulates human iron metabolism. It is believed that in response to inflammatory cytokines, such as IL-6, the liver produces increased amounts of hepcidin which, in turn, prevents the protein ferroportin from stimulating release of stored iron.
Ideally, AI is resolved by successful treatment of the chronic disease with which the AI is associated. Unfortunately, such chronic conditions may be refractory to treatment, and many patients live with AI as part of their overall health problems. In more severe cases, blood transfusions, or commercially-produced erythropoietin, can be helpful in some circumstances, although both treatments are costly, and may be dangerous (see, e.g., Zarychanski R, Houston D. S., Can. Med. Assoc. J. 179 (4): 333-7 (2008)). Intravenous infusion of iron has also been used to treat AI, although the iron compounds that are infused may be potent oxidants which are potentially harmful to the body (see, e.g., R. A. Zager, Clin. J. Am. Soc. Nephrol. 1 Suppl 1: S24-31 (Sep. 2006)).
Thus, there is a continuing need for compositions and methods for treating, preventing, and/or ameliorating one or more symptoms of AI.